Disease relevance of Enah

• The association of Mena with the surface of the intracellular pathogen Listeria monocytogenes and the G-actin binding protein profilin suggests that this molecule may participate in bacterial movement by facilitating actin polymerization [1].
• Profilin II-GFP co-localised with vinculin and Mena to the focal adhesions in REF-52 fibroblasts and was distributed as a thin line at the front of protruding lamellipodia in B16-F1 mouse melanoma cells [2].
• Expression of NDPP-1 was also detected in embryonic carcinoma and pheochromocytoma cell lines, but not in fibroblasts [3].
• The effect of 2 hypoxic cell radiosensitizers, misonidazole and NDPP, on the O2 consumption of Ehrlich ascites tumour cells was compared in media with and without glucose [4].

Psychiatry related information on Enah

• Further characterization of the FE65-Mena complex may identify a physiological role for these proteins in beta-amyloid precursor protein biogenesis and may help in understanding the mechanism of molecular changes that underlie Alzheimer disease [5].

High impact information on Enah

• In keratinocytes either null for alpha-catenin or blocked in VASP/Mena function, filopodia embed, but actin reorganization/polymerization is prevented, and membranes cannot seal [6].
• The crystal structure of the mammalian Enabled (Mena) EVH1 domain complexed with a peptide ligand reveals a mechanism of recognition distinct from that used by other proline-binding modules [7].
• Expression of neural-enriched isoforms of Mena in fibroblasts induces the formation of abnormal F-actin-rich outgrowths, supporting a role for this protein in microfilament assembly and cell motility [1].
• In primary neurons, Mena is concentrated at the tips of growth cone filopodia [8].
• Mammalian enabled (Mena) is a member of a protein family thought to link signal transduction pathways to localized remodeling of the actin cytoskeleton [8].

Biological context of Enah

• Mice deficient in either Mena or VASP exhibit subtle defects in forebrain commissure formation and platelet aggregation, respectively [9].
• Mutational analysis demonstrated that the phosphorylation site of Mena is Tyr-296 [10].
• Using complementation of phenotypes in Ena/VASP-deficient cells and overexpression in normal fibroblasts, we have assayed the function of a panel of mutants in one member of this family, Mena, by mutating highly conserved sequence elements found in this protein family [11].

Anatomical context of Enah

• Mena-deficient mice are viable; however, axons projecting from interhemispheric cortico-cortical neurons are misrouted in early neonates, and failed decussation of the corpus callosum as well as defects in the hippocampal commissure and the pontocerebellar pathway are evident in the adult [8].
• Finally, we demonstrated that Mena binds to FE65 in vivo by coimmunoprecipitation assay from COS cell extracts [5].
• VASP and Mena, substrates of cyclic nucleotide-dependent protein kinases, are associated in different cell types with microfilaments, focal adhesions, cell-cell contacts, and highly dynamic membrane regions [12].
• In intestine and stomach, prominent VASP and Mena immunoreactivity is detected in intestinal smooth muscle cells and blood vessels and cellular membranes of epithelial cells [12].
• In kidney, VASP and Mena are abundantly expressed in glomerular mesangial cells and in papilla [12].

Associations of Enah with chemical compounds

• Fat was shown to be significantly downregulated (P=0.027), and Catnb and Enah were significantly upregulated (P=0.0003 and 0.005, respectively), in response to therapeutic doses of lithium [13].
• Abl interactor 1 promotes tyrosine 296 phosphorylation of mammalian enabled (Mena) by c-Abl kinase [10].
• The stimulatory effect of misonidazole and NDPP on O2 utilization in medium with glucose undoubtedly appeared as a release from the Crabtree effect [4].
• A stimulatory effect on O2 consumption was found for 5--20mM misonidazole as well as for 0.5mM NDPP, both in media containing 10(-2)M glucose [4].

Physical interactions of Enah

• Mena binds directly to Profilin, an actin-binding protein that modulates actin polymerization [8].

Other interactions of Enah

• In this study, we investigated the consequence of deleting both Mena and VASP [9].
• Our functional data, substantiated by structural data, demonstrate that the ligand-binding of the Vesl EVH1 domain differs from the interaction characteristics of the previously examined EVH1 domains of the Evl/Mena proteins [14].
• IRSp53 is colocalised with WAVE2 at the tips of protruding lamellipodia and filopodia independently of Mena [15].
• VASP and Mena immunoreactivity in heart is associated with blood vessels and with the intercalated discs of cardiac myocytes, where they colocalize with connexin-43 [12].

Analytical, diagnostic and therapeutic context of Enah

• The reverse transcriptase-polymerase chain reaction analysis of mRNA from adult mouse tissues indicated that heart and testis expressed this gene (named NDPP-1) at relatively high levels, while lower levels of mRNA were detected in a number of other tissues [3].

References